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Despite a therapeutic option for severe acute respiratory distress syndrome (ARDS), the survival benefit of venovenous extracorporeal membrane oxygenation (VV-ECMO) is still controversial in adults. This study was aimed at investigating the prognostic factors for ECMO-treated ARDS in adult patients.From 2012 to 2015, 49 patients (median age: 57 years) received VV-ECMO in our institution and were included in this retrospective study. The indication of VV-ECMO was a severe hypoxemia (PaO2/FiO2 ratio <70 mmHg) under mechanical ventilation (MV) with a peak inspiratory pressure (PIP) >35 cmH2O and a FiO2 >0.8. To decrease the impact of pulmonary injuries associated with the high-pressure ventilation, the settings of MV on VV-ECMO were downgraded according to our protocol. Outcomes of this study were death on VV-ECMO and death in hospital. Important demographic and clinical data during the treatment were collected for outcome analyses.All patients experienced significant improvements in arterial oxygenation on VV-ECMO. Twenty-four hours after initiation of VV-ECMO, the median PaO2/FiO2 ratio increased from 58 to 172 mmHg (P < 0.001) and the median SaO2 increased from 86% to 97% (P < 0.001). In the meantime, the MV settings were also effectively downgraded. The median PIP decreased from 35 to 29 cmH2O (P < 0.001) and the median tidal volume decreased from 7 to 5 ml/kg/min (P < 0.001). Twelve patients died during the treatment of VV-ECMO and 21 patients died before hospital discharge. Among all of the pre-ECMO variables, the pre-ECMO pulmonary dynamic compliance (PCdyn) <20 mL/cmH2O was identified to be the prognostic factor of death on VV-ECMO (odds ratio [OR]: 6, 95% confidence interval [CI]: 1–35, P = 0.03), and the pre-ECMO duration of MV >90 hours was the prognostic factor of death before hospital discharge (OR: 7, 95% CI: 1–29, P = 0.01).VV-ECMO was a useful salvage therapy for severe ARDS in adults. However, the value of PCdyn and the duration of MV before intervention with VV-ECMO may significantly affect the patients’ outcomes.

Venovenous extracorporeal life support (VV-ECLS) is a lifesaving but invasive treatment for acute respiratory failure (ARF) that is not improved with conventional therapy. However, using VV-ECLS to treat ARF in adult cancer patients is controversial.This retrospective study included 14 cancer patients (median age: 58 years [interquartile range: 51–66]; solid malignancies in 13 patients and hematological malignancy in 1 patient) who received VV-ECLS for ARF that developed within 3 months after anticancer therapies. VV-ECLS would be considered in selected patients with a PaO2/FiO2 ratio ≤70 mmHg under advanced mechanical ventilation.Before ECLS, the medians of intubation day, PaO2/FiO2 ratio, and Sequential Organ Failure Assessment (SOFA) score were 8 (2–12), 62 mmHg (53–76), and 10 (9–14), respectively. The case numbers of bacteremia, thrombocytopenia (platelet count <50000 cells/μL), and neutropenia (actual neutrophil count <1000 cells/μL) detected before ECLS were 3 (21%), 2 (14%), and 1 (7%), respectively. After 24 hours of ECLS, a significant improvement was seen in PaO2/FiO2 ratio but not in SOFA score. Six patients experienced major hemorrhages during ECLS. The median ECLS day, ECLS weaning rate, and hospital survival were 11 (7–16), 50% (n = 7), and 29% (n = 4). The development of dialysis-dependent nephropathy predicted death on ECLS (odds ratio: 36; 95% confidence interval: 1.8–718.7; P = 0.01). With a median follow-up of 11 (6–43) months, half of the survivors died of cancer recurrence and the others were in partial remission.The most prominent benefit of VV-ECLS is to improve the arterial oxygenation and rest the lungs. This may increase the chance of recovery from ARF in selected cancer patients.

BackgroundHigh-tidal-volume mechanical ventilation used in patients with acute lung injury (ALI) can induce the release of inflammatory cytokines, as macrophage inflammatory protein-2 (MIP-2), recruitment of neutrophils, and disruption of alveolar epithelial and endothelial barriers. Induced pluripotent stem cells (iPSCs) have been shown to improve ALI in mice, but the mechanisms regulating the interactions between mechanical ventilation and iPSCs are not fully elucidated. Nuclear factor kappa B (NF-κB) and NF-κB repressing factor (NKRF) have been proposed to modulate the neutrophil activation involved in ALI. Thus, we hypothesized intravenous injection of iPSCs or iPSC-derived conditioned medium (iPSC-CM) would decrease high-tidal-volume ventilation-induced neutrophil infiltration, oxidative stress, and MIP-2 production through NF-κB/NKRF pathways.MethodsMale C57BL/6 mice, aged between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal-volume (30 ml/kg) mechanical ventilation with room air for 1 to 4 h after 5×107 cells/kg mouse iPSCs or iPSC-CM administration. Nonventilated mice were used as control groups.ResultsHigh-tidal-volume mechanical ventilation induced the increases of integration of iPSCs into the injured lungs of mice, microvascular permeability, neutrophil infiltration, malondialdehyde, MIP-2 production, and NF-κB and NKRF activation. Lung injury indices including inflammation, lung edema, ultrastructure pathologic changes and functional gas exchange impairment induced by mechanical ventilation were attenuated with administration of iPSCs or iPSC-CM, which was mimicked by pharmacological inhibition of NF-κB activity with SN50 or NKRF expression with NKRF short interfering RNA.ConclusionsOur data suggest that iPSC-based therapy attenuates high-tidal-volume mechanical ventilation-induced lung injury, at least partly, through inhibition of NF-κB/NKRF pathways. Notably, the conditioned medium of iPSCs revealed beneficial effects equal to those of iPSCs.

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BackgroundVenovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS.MethodsThis retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality.ResultsThe causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079–1.565, p < 0.001) was found to be the only baseline ventilator parameter that independently affected the hospital mortality in these ECMO-treated patients.ConclusionSince the duration of MV before ECMO institution was strongly correlated to the outcome of adult respiratory ECMO, medical centers are suggested to find a suitable prognosticating tool to determine the starting point of respiratory ECMO among their candidates with different duration of MV.Trial registrationThis study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601483B0) on November 23, 2016. All of the data were extracted from December 1, 2016, to January 31, 2017.

Although aerosol delivery through mechanical ventilators has been used to administer various medications, little is known of administration with colistin. This in vitro evaluation aimed to evaluate size distribution of colistin delivery by different types of nebulizers and concentrations during mechanical ventilation. Colistin methanesulfonate (colistin) for injection was dissolved in 6 mL of distilled water to produce a low concentration (L; 156 mg) and a high concentration (H; 312 mg). A dose volume of 6 mL was placed in a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN). The inhaled mass (mean ± SD) of the VMN-L (53.80 ± 14.79 mg) was greater than both the JN-L (19.82 ± 3.34 mg, P = 0.001) and JN-H (31.72 ± 4.48 mg, P = 0.017). The nebulization time of the VMN-L (42.35 ± 2.30 min) was two times longer than the JN-L (21.12 ± 0.8 min) or JN-H (21.65 ± 0.42 min; P < 0.001). The mass median aerodynamic distal to the endotracheal tube was within a similar range at 2.03 to 2.26 μm (P = 0.434), independent of neb or formulation concentration. In conclusion, the VMN-L yields greater inhaled mass than the JN with either concentration. Therefore, a standard nominal dose of colistin results in a higher delivered dose during mechanical ventilation with a VMN compared with a JN and may be considered the preferred device. If JN must be used, multiple doses of low concentration colistin may compensate for poor delivery performance.

Malnutrition is associated with adverse outcomes in patients with liver cirrhosis. Relevant data about nutrition risk in critically ill cirrhotic patients are lacking. The modified Nutrition Risk in Critically Ill (mNUTRIC) score is a novel nutrition risk assessment tool specific for intensive care unit (ICU) patients. This retrospective study was conducted to evaluate the prevalence and prognostic significance of nutrition risk in cirrhotic patients with acute gastroesophageal variceal bleeding (GEVB) using mNUTRIC scores computed on admission to the intensive care unit. The major outcome was 6-week mortality. One-hundred-and-thirty-one admissions in 120 patients were analyzed. Thirty-eight percent of cirrhotic patients with acute GEVB were categorized as being at high nutrition risk (a mNUTRIC score of ≥5). There was a significantly progressive increase in mortality associated with the mNUTRIC score (χ2 for trend, p < 0.001). By using the area under a receiver operating characteristic (ROC) curve, the mNUTRIC demonstrated good discriminative power to predict 6-week mortality (AUROC 0.859). In multivariate analysis, the mNUTRIC score was an independent factor associated with 6-week mortality. In conclusion, the mNUTRIC score can serve as a tool to assess nutrition risk in cirrhotic patients with acute GEVB.